Neuromuscular Blockade Drug Flashcards Preview

Anesthesia Pharm I > Neuromuscular Blockade Drug > Flashcards

Flashcards in Neuromuscular Blockade Drug Deck (41)
1

what is the action of NMB drugs?

prevents muscle contraction by interfering with the transmission of an action potential from the nerve ending to the muscle
*also known as relaxants, paralytics, NM antagonists

2

what are some uses of NMBs?

*facilitate endotracheal intubation
*allow balanced anesthesia without patient movement
may not have to use as much gas since NMB keeps
patient still, gas only needed for sedation; less gas
can be breathed off quicker, allowing to wake up and
move faster
-decrease muscle tone to provide appropriate operating conditions
(large abd/GI cases, esp during suturing, prevents
hernia and complication)
-alleviate muscle activity during ECT so induced seizure is localized to the desired area in the brain
-assist in controlled long-term vent patients in ICU (ARDS, increased peep)

3

what is the site of function for NMBs?

at the junction between the nerve ending and muscle

4

Describe normal NM function.

-impulse arrives at the motor nerve terminal
-Ca++ influx cause vesicles holding Ach to line up at the presynaptic membrane right across from the muscle
-vesicles rupture and release Ach which diffuses the short distance across the synaptic cleft to the postsynaptic or postjunctional nicotinic (cholinergic)muscle receptors
-Ach binds with 2 alpha sites on postjunctional receptors causing the opening of the ion channel
-Na+ and K+ ions move through the channel causing depolarization (Na+ moves inside the membrane increasing the membrane potential from rmp -90mV to threshold of -45mV)
-Action potential spreads over the surfaces of the muscle fibers causing contraction

5

How is Ach action terminated?

-Ach either quickly diffuses away or is metabolized
-AChE waits right outside of the ACh receptors in the postjunctional membrane
-Hydrolyzes ACh rapidly, resulting in a short depolarization and a rapid repolarization of the muscle cells

6

What role does Ca++ play in NM function and how does Magnesium compare?

-Ca++ influx causes the vesicle holding ACh to align, promoting ACh release
*Magnesium has the OPPOSITE effect of Ca++
*Ca++ toxemia treated with Mag sulfate
*if Ca++ is LOW, ACh cant release and results in muscle weakness
*if Mag is HIGH, it will mimic low Ca++ effects, causing muscle weakness
-if and OB patient is put on a Mag drip, expect the need for LESS NMB

7

What is ACh?

-main neurotransmitter in NM function
-synthesized in the motor nerve ending by acetylation of choline which is controlled by choline acetylase enzyme
-rapidly hydrolyzed by AChE to acetic acid and choline
*choline is taken back into the nerve ending to be used to make more ACh

8

Describe the prejunctional or presynaptic ACh receptors.

-located on the nerve ending
-affects the neurotransmitter release
-Ion channel opening allows the influx of Na+ and Ca++
-activation mobilizes additional ACh for subsequent release
*blockade of these receptors cause a decrease in the release of ACh resulting in the tetanic fade

9

Describe extrajunctional or perijunctional ACh receptors.

-found throughout the muscle cell
-similar to what is found on fetal muscle cells, but as the cell matures, these receptors fade away
-play no role in NM contraction
-if the muscle is not being used, these receptors proliferate (come back)
*seen with damaged, diseased, or denervated muscle like with burns, paralysis, stroke, immobilization, and some muscular dystrophies
*these receptors allow channels to stay open 4x longer

10

What effect does extrajunctional receptors have on NMBs?

-Ach or nondepolarizing NMBs may become "distracted" and bind to extrajunctional receptors rather than postjunctional receptors where their block is desired
-with the depolarizing agent SCh, ion channels are also opened at extrajunctional receptors causing Na+ and Ca++ to move in and K+ to move out; however since these ions channels stay open 4x longer, continued K+ efflux leads to severe hyperkalemia

11

When should you be cautious of extrajunctional receptors and not use a depolarizing agent (SCh)?

-past the 48 hour mark of a severe burn
-usually avoided in pediatric patients, esp. males age 4 and under, due to a high risk of undiagnosed muscular dystrophy
*hyperkalemia can lead to asystole in these patients

12

Describe postjuctional or postsynaptic receptors.

-located in the junctional folds of the muscle membrane aligned across from area where presynaptic vesicles release ACh
-made up of 5 linear protein subunits: 2 alpha, beta, delta, and epsilon which reach from extra- to intracellular and form a channel for Na+, K+, and Ca++ flow
-ACh must bind to the extracellular sites on the 2 alpha subunits causing the receptor to change and open a channel for cations (+ ions) to flow through
-Ca++ and Na+ influx as K+ effluxes creating a change in the transmembrane potential and depolarization occurs causing muscle contraction
*BOTH alpha subunits must be bound to ACh for action

13

Where are the specific sites of action for NMB agents?

-The binding sites of the alpha subunits are the sites of action for both nondepolarizing and depolarizing agents
-SCh attaches to the alpha sites and mimic the action of ACh causing depolarization, BUT not metabolized as quickly so stay on receptor blocking repolarization or more depolarization
-nondepolarizing agents attach to one alpha subunit to prevent ACh from binding, thus preventing depolarization
*only need to block one, since both units must be bound to ACh for action

14

Describe channel blockade.

-besides acting on alpha subunits, some drugs can physically block an open channel or a closed channel around the extracellular surface
*antibiotics, quinidine, tricyclic antidepressants, and naloxone
*local anesthetics have this MoA which blocks the Na+ channel, blocking sensory

15

time from administration to maximum effect

onset time

16

time from administration to 25% recovery of twitch response

clinical duration

17

time from administration to 90% recovery of twitch response (without reversal)

total duration

18

time from 25% to 75% recovery of twitch response

recovery index (usually take more time to receive the first 25% twitch, but reach 75% quicker once 25% is achieved)

19

the dose needed to produce 95% suppression of single twitch response (potency)

ED95 (effective dose)

20

usually 2-3 times the ED95

intubating dose

21

What are the objectives of clinical monitoring of NMB?

-titration of dosage to desired effect
-monitor for unusual resistance or sensitivity or prolonged action of NMB
-evaluation of reversibility
-determine recovery from block in conjunction with clinical evaluation

22

How does NMB monitoring work?

-electrical stimulation of the peripheral motor nerve to observe the muscular contractions in response
*adult muscles have one NMJ per muscle cell except with the extraocular and facial muscles which have multiple innevations
*always place the black lead over the nerve
*ensure that the lead does not become a pressure point

23

What will you look for with ulnar nerve stimulation.

adduction of the thumb via the adductor pollicis brevis muscle
-located lateral to the flexor carpi ulnaris tendon and medial to the ulnar artery

24

Describe monitoring of the posterior tibial nerve

*when stimulated, causes plantar flexion of the great toe
-may use with head cases and when arms are tucked
-located behind the medial maleous of the tibia and posteromedial to the p.t. artery

25

Describe monitoring of the lateral popliteal (peroneal) nerve

*when stimulated, the foot will dorsiflex
-located behind the head of the fibula and around the neck of the fibula

26

Describe facial nerve monitoring

*stimulation causes response in the orbicularis oculi or the frontalis muscles
*place electrodes close to the tragus of the ear, be careful not to directly stimulate the superficial face muscles

27

What is significant about the orbicularis oculi muscle?

-small and rapidly moving muscle and highly vascularized similar to the laryngeal muscle
-a greater density of ACh receptors cause a less dense block, making this muscle recovery more rapidly than others
*reflects the onset of laryngeal muscle relaxation
*possible to OD relaxant and overestimate recovery if only looking at the OO

28

In what order do muscles have onset of relaxation?

-first, small rapidly moving muscles that are highly vascularized: OO and laryngeal muscles
-second, the trunk and abdominal, and long muscles with mostly slow fibers such as the adductor pollicis
-final onset is the intercostal and diaphragm muscle which may be a concern with reflux patients and coughing

29

in what order do muscles recover?

-diaphragm recovers first (it is very resistant to NMB)
-rapidly moving muscles (eyes and fingers) are next
-last to recover are long muscle

30

What are the first signs of relaxation if NMB are given to a conscious patient?

-inability to focus vision or keep eyelids open causing double vision (rapidly moving muscles first)
-inability to swallow
-inability to phonate (speak)
*sometimes will need to give a small dose (1/10) for slight relaxation but this can possibly cause major effects with major diagnoses like myasthenia gravis
*hearing acuity is intensified as small muscles of the middle ear are relaxed

31

Describe single twitch stimulus.

*may be ok to use for monitoring of onset not useful for recovery since return to control height does not mean complete recovery from blockade
*need to know the baseline before giving relaxant
-uses frequency between 0.1 Hz (1 stimulus every 10sec) and 4 Hz (4 stimuli every 1 sec)
-after the administration of a nondepolarizer, the amplitude of subsequent twitches decrease in magnitude as the frequency increases

32

Describe train of four.

*useful for maintenance of NMB along with clinical signs of relaxation
-the delivery of four stimuli at a frequency of 2 Hz (four stimuli in 2 sec)
-technique relies on the reduction of ACh release with rapid rates of stimulation (wait 10-12 sec before repeating)
*produces a ratio of the fourth twitch to the first twitch
*with recovery, cant really tell the difference between a ratio of 1:1 and 1:0.6

33

Describe TOF fade.

-with the initiation of blockade, all twitches decrease and disappear together due to decreasing release of ACh
-Twitch 1 returns gradually
-2/4 means 90% block
-3/4 means 80% block
-4/4 means 70-75% block
*clinical relaxation requires 75-90% block

34

a TOF of > 0.6 what do you look for?

-patient should be able to sustain headlift more than 3 seconds
*really want them to hold 5 seconds
-requires cooperation
*for babies, look for a leg lift for 5 seconds

35

how does TOF present with NMB?

-with a depolarizing block (SCh), all four twitches are reduced
-with a nondepolarizing block, the TOF ratio decreases or fades and is inversely proportionate to the degree of block
-if TOF fade occurs during the administration of SCh, it is a sign of phase II block

36

describe double-burst.

*used during maintenance phase
-gives two short bursts of three stimuli at a frequency of 50 Hz separated by 750ms
-each burst represents 1st twitch and 4th twitch
-amplifying allows to see the difference and ratio between the first and fourth twitch
*easier to detect fade than with TOF

37

describe tetanic stimulation.

*used to assess recovery
-stimulation of 50 Hz to 100 Hz
-if no fade on TOF, check tetanus for 5 seconds
*HURTS- do not use if surgeon is still stitching
*must wait 10 minutes after stimulation to avoid false reading due to large stimulation and extreme release of ACh that may still be active
*USE LAST

38

posttetanic twitch

*used to anticipate how long before patient is reversible
*must have 1 twitch to be reversed
-5 second 50 Hz tetanus, then 3 second pause, then twitch stimuli at 1 Hz (or just do TOF)
-after the tetanus stimulation, there is an increase in mobilization of ACh which allows increase in the twitch response
-if tetanic stimulation elicits no response, the posttetanic twitch might be elicited to estimate time until reversible
*posttetanic twitch of 10 coincides with first twitch TOF
*posttetanic of 1 means average time to first twitch of TOF for a long acting blocker of 30 min and 8 min for an intermediate blocker

39

what are the guidelines for reversal of NMB?

-if no twitch, do not attempt reversal b/c antagonism will be difficult, potentially prolonged, and unpredictable
-with only one twitch in TOF, adequate reversal may take as long as 30 min
-with 2-3 twitches, reversal may take from 4-12 minutes based on the relaxant
-with 4 twitches, recovery can be achieved within 5 min (neostigmine) or 2-3 min (edrophonium)
-if no fade of twitches, 70-75% receptors blocked (only 70% block is fully recovered)

40

what are some considerations of clinical monitoring?

*assess baseline after induction, but before NMB
*do not intubate until twitch is essentially absent
*after SCh, check recovery prior to giving a nondepolarizing NMB
*maintain 1-2 twitches during the case
-avoid using nerve stimulator on paralyzed limb
-peripheral muscles have a denser block than those monitored at the facial nerve
*don't reverse unless you have one twitch
*use TOF (double burst) and sustained tetanus (in that order) to assess fade after reversal

41

what are some conditions for nerve stimulation?

-0.2 ms rectangular pulse
-firmly place moist electrodes on clean, dry, defatted, warm skin
-ulnar nerve stimulation, abduct the thumb to feel the adductor pollicis twitch
*negative (black) lead is placed directly over the nerve